Identification and expression of novel isoforms of human stromal cell-derived factor 1

Stromal Cell-derived factor 1 (SDF-1) is a CXC chemokine that binds to the CXCR4 receptor. Recent publication indicates that the SDF-1/CXCR4 signaling pathway plays a pivotal role during development and in many patho-physiological conditions including hematopoiesis, blood vessel formation, cancer metastasis, angiogenesis and HIV infection. Two human SDF-1 isoforms, SDF-1 alpha and SDF-1 beta, have been reported to date. Here we report the identification of four additional human SDF-1 isoforms derived from alternative splicing events, SDF-1 gamma, SDF-1 delta, SDF-1 epsilon and SDF-1 phi. These SDF-1 splice variants all share the same first three exons but contain different fourth exons. The human SDF-1gene spans over 88 kilobase-pairs on chromosome 10. Using the semi-quantitative RT-PCR method, we determined the tissue distribution of these SDF-1 isoforms. SDF-1 alpha and SDF-1 beta share similar expression patterns and the highest expression were detected in liver, pancreas and spleen. SDF-1 gamma seems to be the human orthologue of recently isolated rat SDF-1 gamma, and its expression was only detected in the heart. SDF-1 delta expression can be detected in several adult tissues but the highest expression was detected in fetal liver. When transfected into HEK293 cells, all the SDF-1 isoforms can be detected as secreted proteins in the cell culture media. The conditioned media from transfected cells can stimulate cell migration in a CXCR4-dependent manner. These data suggest that the novel SDF-1splice variants encode functional proteins. (c) 2006 Elsevier B.V. All rights reserved.